The function of the animal core is to provide services in many aspects of this program project, including projects 1 and 2. It will breed the compound heterozygous lines carrying the mouse alpha and mouse beta knockouts and human alpha and beta/S transgenes to produce mice exclusively expressing human HbS. To date, we have generated such a mouse model. However, the high mortality at prenatal or neonatal life due to the severe anemia results in the low frequency of its production, at approximately one out of 500 mice bred. In order to improve the efficiency, we will make several new transgenic lines to rescue the model from its lethality in perinatal stage. This core will maintain these animals and provide them to the investigators for testing pharmacological agents in Project 1. It will also provide pregnant mice carrying embryos with certain genetic defect to test the efficiency of gene transfer in Project 2.